Staphylococci have become the most common cause of nosocomial infections and greater than 25% of preterm infants have documented staphylococcal sepsis. We have developed a humanized monoclonal antibody that promotes enhanced bacterial clearance and survival in adult and neonatal animal models of S. epidermidis and S. aureus sepsis. We propose to study the mechanism of protective activity and to provide information and material that will assist us in planning clinical studies. Using animal sepsis models we will study the relationship of dose and time of antibody injection to survival after the inoculation of antibiotic resistant and sensitive strains of S. epidermidis and S. aureus. To develop other models that show enhanced susceptibility to staphylococcus infections which we can use to test the efficacy of our antibody we will study mice that are deficient in complement or in B, T or NK cells. In preparation for clinical studies we will standardize an in vitro assay to detect ng-pg/ml concentrations of our humanized antibody in human sera. Finally we will develop cell lines that produce high levels of humanized antibody and use a hollow fiber system for large scale production and purification for preclinical testing. Antibody will be utilized for human tissue cross reactivity determination and pharmacokinetics in non human primates. PROPOSED COMMERCIAL APPLICATIONS: Nosocomial infections occur in 1.75-3 million patients, each year causing significant morbidity and mortality. Specifically there are between 100,00() and 400,000 bloodstream infections annually in the US and 25,000-1 00,000 patients die as a direct result of nosocomial sepsis. Nosocomial infections, staphylococci being the most common microbial pathogens, increase the cost of health care by $4.5-15 billion annually. Prevention of staphylococcal sepsis would be of great medical and economic value.